Rezafungin and echinocandins

Rezafungin: CD101, Rezzayo. Class members: caspofungin (Cancidas), micafungin (Mycamine), anidulafungin (Eraxis/Ecalta)

Antimicrobial & antiviral

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Note on this profile. The echinocandins are approved, hospital-administered prescription antifungals. This page explains the published science. Community or self-directed use is essentially none documented and would be clinically meaningless for a healthy person.

Summary

Class: Cyclic lipopeptides: a six-amino-acid ring (several non-standard hydroxylated amino acids) attached to a long fatty-acid or aryl side-chain; semi-synthetic derivatives of fungal fermentation products. Rezafungin is a structural analogue of anidulafungin with a choline-aminal modification that confers stability
Mechanism: Non-competitively inhibit β-(1,3)-D-glucan synthase, an enzyme fungi need to build their cell wall and humans do not have, causing fungal cell lysis
Routes studied: Intravenous only (the molecules are too large and poorly absorbed for oral use); rezafungin also studied subcutaneously and topically in early work
Half-life: Caspofungin ~9–11 h; micafungin ~11–17 h; anidulafungin ~24–26 h; rezafungin ~130–150 h, which is what allows once-weekly dosing
Storage: Lyophilised vials refrigerated (caspofungin) or room temperature (micafungin, anidulafungin, rezafungin) per label; reconstituted solutions used promptly by hospital pharmacy
Regulatory status: All four approved medicines (rezafungin US 2023, EU 2023, UK 2024 †)

Doses are as reported in studies or by the community — never recommendations.

1What it is

Echinocandins are antifungal antibiotics whose core is a cyclic hexapeptide produced by soil fungi (echinocandin B from Aspergillus nidulans, pneumocandin from Glarea lozoyensis, FR901379 from Coleophoma empetri). Chemists swapped the natural fatty tail for synthetic side-chains to improve solubility and safety, producing caspofungin (approved 2001), micafungin (2005) and anidulafungin (2006). They became first-line treatment for candidaemia because they kill Candida rapidly, work against azole-resistant strains and have very few drug interactions.

Rezafungin is the first new echinocandin in nearly two decades. A single chemical change at a fragile position in the anidulafungin ring stops it from degrading in the body, extending the from one day to around a week. It was approved in the US in March 2023 and in the EU in December 2023 for candidaemia and invasive candidiasis in adults with limited treatment options (the EU indication is not restricted in this way †).

2How it's thought to work

β-(1,3)-D-glucan is a major structural polymer in the cell walls of Candida, Aspergillus and Pneumocystis. Echinocandins bind the Fks1 subunit of the synthase enzyme on the fungal cell membrane and block polymer production.

Against Candida the effect is fungicidal (the wall fails under osmotic pressure); against Aspergillus it is fungistatic, damaging only the growing hyphal tips.

They do not act on Cryptococcus, most moulds other than Aspergillus, or the endemic dimorphic fungi, which limits their spectrum.

Resistance arises through point mutations in the FKS genes, and is a growing concern in Candida glabrata and Candida auris.

An echinocandin blocking beta-1,3-glucan synthase in the fungal membrane. The glucan that gives a fungal cell wall its strength is not made; because human cells have no such wall, the target does not exist in the host.Schematic — not to scale

3What the research shows

Candidaemia and invasive candidiasis

Caspofungin was non-inferior to amphotericin B (Mora-Duarte 2002, NEJM). Micafungin was non-inferior to liposomal amphotericin B (Kuse 2007, Lancet) and to caspofungin (Pappas 2007, Clin Infect Dis). Anidulafungin was statistically superior to fluconazole in the primary analysis (75.6% vs 60.2% global response; Reboli 2007, NEJM). Rezafungin was non-inferior to caspofungin in ReSTORE (199 patients; day-30 all-cause mortality 24% vs 21%; mycological eradication at day 14 59% vs 61%) (Thompson 2023, Lancet). [1][2][3][4][5]

Prophylaxis after stem-cell transplant

Micafungin was superior to fluconazole for preventing invasive fungal infection during neutropenia (van Burik 2004, Clin Infect Dis). Rezafungin's ReSPECT trial (around 460 allogeneic transplant recipients) compared weekly rezafungin against standard azole prophylaxis for Candida, Aspergillus and Pneumocystis combined; topline results were announced in 2024–2025 and the outcome should be checked before publication †. [6]

Oesophageal candidiasis

All three older agents were effective versus fluconazole or amphotericin in .

Invasive aspergillosis

Caspofungin is approved as salvage therapy on the basis of an open-label study (Maertens 2004, Clin Infect Dis); echinocandins are not first-line for Aspergillus. Combination with voriconazole showed a trend toward lower mortality in one RCT (Marr 2015, Ann Intern Med). [7]

4Reported side effects and interactions

Literature-reported

Generally among the best-tolerated antifungals. Common: fever, phlebitis at the infusion site, nausea, headache, raised liver enzymes (typically mild), hypokalaemia. Histamine-mediated infusion reactions (flushing, rash) if infused too fast, mainly with caspofungin and anidulafungin. Rezafungin additionally carried signals of tremor and photophobia at higher doses in early studies, and a label note about these neurological effects †. Rare hepatotoxicity; micafungin carries an EU warning about liver tumours in rats at high doses with uncertain human relevance.

Community-reported

none documented.

Theoretical. emergence of FKS-mutant resistant Candida with widespread use.

Interactions. few, which is a major advantage. Caspofungin levels fall with rifampicin, phenytoin, carbamazepine and other inducers (dose increase to 70 mg daily recommended) and rise with ciclosporin (with liver enzyme increases). Micafungin modestly raises sirolimus, nifedipine and itraconazole levels. Anidulafungin and rezafungin have essentially no clinically relevant interactions.

Markers researchers commonly monitor

Per labels and infectious-disease practice:

Marker	Why it's watched
Liver enzymes (ALT, AST, bilirubin)	the main laboratory safety signal for all echinocandins.
Blood cultures (repeat until negative)	the primary efficacy marker in candidaemia; defines the start of the treatment clock.
Serum β-D-glucan	a fungal biomarker that falls with successful treatment; also used in diagnosis.
Potassium	hypokalaemia is reported.
Ciclosporin and tacrolimus levels	in transplant recipients receiving caspofungin or micafungin.
Antifungal susceptibility (MIC) and FKS genotyping	in treatment failure or C. glabrata/C. auris infection.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Hospital-pharmacy products. vials are with sterile water or saline and diluted into an infusion bag; infusion over about one hour (rezafungin and caspofungin), with slower rates if infusion reactions occur. Anidulafungin solution must not be frozen. None of these is a self-administered medicine and the calculator does not apply.

6Commonly studied alongside

Compared with fluconazole, voriconazole and amphotericin B formulations. Studied in combination with voriconazole for aspergillosis. Not studied with any research peptide. Related peptide antimicrobials on this site: vancomycin and the glycopeptides (profile #227), daptomycin (a lipopeptide antibacterial), polymyxins, bacitracin.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	All four FDA-approved. Rezafungin (Rezzayo) approved March 2023 for candidaemia and invasive candidiasis in adults with limited or no alternative options; prophylaxis indication pending ReSPECT review †
European Union	Caspofungin, micafungin, anidulafungin EMA-authorised. Rezafungin authorised December 2023 for invasive candidiasis in adults
United Kingdom	Caspofungin, micafungin, anidulafungin MHRA-licensed. Rezafungin licensed 2024 †
Australia	Caspofungin, micafungin, anidulafungin TGA-registered. Rezafungin †
South Africa	Caspofungin, micafungin and anidulafungin SAHPRA-registered. Rezafungin †
Sport (WADA)	Not prohibited

8Open questions

Does rezafungin's weekly dosing enable outpatient treatment of invasive candidiasis and reduce hospital stays? Trials measured non-inferiority, not this.
How fast will FKS-mediated resistance spread with prophylactic use?
Can a once-weekly echinocandin replace azole prophylaxis in transplant and leukaemia patients, given the ReSPECT result?

9References

1Thompson GR 3rd et al. (2023). Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial. Lancet. PubMed · DOI
2Mora-Duarte J et al. (2002). Comparison of caspofungin and amphotericin B for invasive candidiasis. NEJM. PubMed · DOI
3Reboli AC et al. (2007). Anidulafungin versus fluconazole for invasive candidiasis. NEJM. PubMed · DOI
4Kuse ER et al. (2007). Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet. PubMed · DOI
5Pappas PG et al. (2007). Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis. PubMed · DOI
6van Burik JA et al. (2004). Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis. DOI
7Marr KA et al. (2015). Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med. PubMed · DOI
8Denning DW (2003). Echinocandin antifungal drugs. Lancet. PubMed · DOI
9Rezzayo US prescribing information (2023); EMA Rezzayo EPAR (2023). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

31 Oct 2026Profile published — awaiting medical review

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